This ADRC is an integrated unit of Washington University that coordinates and supports the work of established investigators and teachers from diverse backgrounds. Mechanisms are provided for the support of programs and projects with a focus on both clinical and basic science research, and the development of improved training of professionals within the University and outreach programs for health care professionals and the public in the regional community. The clinical theme of the research component in this application is the identification and characterization of mild and very mild dementia of the Alzheimer type (DAT) in comparison with healthy aging.The basic science theme is the characterization of neurobiological principles and mechanisms relevant to aging of the nervous system and neuronal dysfunction and/or death in Alzheimer's disease (AD). Five cores (Biostatistics, Clinical, Psychometric, Neuropathology/Tissue Resource, Administration) will support five projects and five pilots. The topics of the projects include: 1) ApoE clearance receptor in CNS; 2) cellular prion proteins; 3) gene expression and neuronal vulnerability in neurodegenerative disease; 4) molecular genetics of dementia; and 5) processing speed, working memory and fluid cognitive abilities in DAT. The pilots study: 1) structure of the A-beta-protein; 2) AD and fibroblast bradykinin receptor modulation; 3) an AMPA receptor modulatory site; 4) protein fatty acylation in neuronal growth and remodeling; and 5) cognitive deficits and speech perception in DAT. A Training and Information-Transfer core supports our educational activities. Two Satellite components reach out to African Americans in our community and to the underserved rural areas of our region. This ADRC also interacts with and supports other investigators at this University, funded through other mechanisms, in order to focus attention on issues relevant to aging, AD and other dementias. Finally, the ADRC interacts with other Centers and the Alzheimer's Association to coordinate our efforts.